Xenobiotic metabolism, oxidant stress and chronic pancreatitis. Focus on glutathione

Chronic pancreatitis, although relatively rare in the Western World, is common in certain tropical zones where staple crops such as cassava are rich in cyanogenic glycosides. This paper reviews the evidence for a cyanide connection, with reference to experimental studies using another plant nitrile, crambene; and then examines the hypothesis that chronic pancreatitis represents a manifestation of uncoordinated detoxification reactions between pancreatic cytochrome P450 mono-oxygenases and phase II conjugating enzymes, resulting in the irreversible consumption of glutathione in the acinar cell. The conclusion is that the central role of disrupted pancreatic glutathione status, as a result of 'xenobiotic stress', in the evolution of chronic pancreatitis cannot be overestimated. This position contrasts with that in acute pancreatitis, in which glutathione depletion has a pivotal role too, but occurs as a result of 'stress' from reactive oxygen species.